Biomarkers in cancer epidemiology: an integrative approach.

There are different reasons for the increase in the use of biomarkers in cancer epidemiology which is as follows: (i) the fact that the identification of new carcinogens, characterized by complex exposure circumstances and weak effects, has become increasingly difficult with traditional epidemiological approaches; (ii) the increasing understanding of mechanisms of carcinogenesis and (iii) technical developments in molecular biology and genetics. While a distinction is made between biomarkers of exposure, intermediate events, disease, outcome and susceptibility, their integration in a unique conceptual model is needed. The use of exposure biomarkers in cancer epidemiology aims at measuring the biologically relevant exposure more validly and precisely. In some instances, there is an obvious improvement in using an exposure biomarker, as in the case of urinary markers of aflatoxin and tobacco-specific nitrosamines. Intermediate (effect) biomarkers measure early--in general non-persistent--biological events that take place in the continuum between exposure and cancer development. These include cellular or tissue toxicity, chromosomal alterations, changes in DNA, RNA and protein expression and alterations in functions relevant to carcinogenesis (e.g. DNA repair, immunological response, etc.). The analysis of acquired TP53 mutations is an example of the potentially important. Biomarkers should be validated and consideration of sources of bias and confounding in molecular epidemiology studies should be no less stringent than in other types of epidemiological studies. The overarching goal is the integration of different types of biomarkers to derive risk and outcome profiles for healthy individuals as well as patients.